Phase 2 study of the lysine-specific demethylase 1 inhibitor bomedemstat for essential thrombocythemia
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: ABSTRACT: Novel treatments that can improve outcomes of essential thrombocythemia (ET) are needed. In a phase 2 trial, participants with ET who required cytoreduction and had inadequate response to, or were intolerant of, ≥1 standard therapy received bomedemstat at a starting dose of 0.6 mg/kg per day, titrated to achieve a target platelet count (200 × 109/L to 400 × 109/L). Primary end points were safety and response, defined as a platelet count of ≤400 × 109/L without new thromboembolic events. Of 73 who received bomedemstat, at 24 weeks, 49 of 64 evaluable participants (77%) achieved a response. Durable reductions in platelet count (≤400 × 109/L for ≥12 weeks) were observed in 52 of 72 participants (72%). Durable reduction in white blood cell count (<10 × 109/L for ≥12 weeks) was observed in 61 of 72 participants (85%); of 10 participants with elevated white blood cell count at baseline, 9 had normal white blood cell count (<10 × 109/L) at week 24. Hemoglobin levels remained stable. After 24 weeks of treatment, a decrease in variant allele frequency of CALR, JAK2, or MPL was observed in 39 of 46 (85%) evaluable participants. By week 24, 2 of 73 participants (3%) had experienced ≥1 thrombotic event, and 15 of 73 (21%) experienced ≥1 hemorrhagic event. During overall treatment period, grade 3 or 4 adverse events (AEs) occurred in 34 of 73 participants (47%). AEs led to temporary treatment interruption in 29 participants (40%) and permanent discontinuation in 11 (15%). No participants died due to AEs. Bomedemstat had clinically relevant activity and manageable safety in participants with ET. This trial was registered at www.clinicaltrials.gov as #NCT04254978.
Source: Blood Advances
Authors: Harinder Gill, Francesca Palandri, David M. Ross, Joachim R. Göthert, Tara Cochrane, Stephen R. Larsen, Anna B. Halpern, Jake Shortt, James M. Rossetti, James Liang, Monia Marchetti, Andrew J. Wilson, Andrew J. Innes, Merit Hanna, Nicola Vianelli, William S. Stevenson, Alessandro M. Vannucchi, Maria Kleppe, Jessica Flynn, Georges Natsoulis, Claire N. Harrison, Hugh Young Rienhoff
Institutions: University of Hong Kong, University of Bologna, South Australia Pathology, Royal Adelaide Hospital, Essen University Hospital, Griffith University, The University of Sydney, Royal Prince Alfred Hospital, University of Washington, Fred Hutch Cancer Center, Monash Medical Centre, Monash Health, Monash University, UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, Middlemore Clinical Trials, Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo, National Health Service, University College London, North Shore Hospital, Waitemata District Health Board, Royal North Shore Hospital, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Merck & Co., Inc., Rahway, NJ, USA (United States)
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,800
Funders: Bristol-Myers Squibb, Pfizer, GlaxoSmithKline, Leukemia and Lymphoma Society, Gilead Sciences, Celgene, AbbVie, Karyopharm Therapeutics, Jazz Pharmaceuticals, Astex Pharmaceuticals, BeiGene, Incyte, Galecto, British Society for Haematology, Novo Nordisk, Astellas Pharma, Swedish Orphan Biovitrum, Grifols, Division of Materials Research, Cilag
OpenAlex ID: W7131820641